Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection.

INTRODUCTION: Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools. METHODS: We tested the efficiency and sensitivity of pooling strategies for RNA extraction and RT-PCR detection of SARS-CoV-2. We tested 184 samples both individually and in pools to estimate the effects of pooling. We further implemented Dorfman pooling with a pool size of eight samples in large-scale clinical tests. RESULTS: We demonstrated pooling strategies that increase testing throughput while maintaining high sensitivity. A comparison of 184 samples tested individually and in pools of eight samples showed that test results were not significantly affected. Implementing the eight-sample Dorfman pooling to test 26 576 samples from asymptomatic individuals, we identified 31 (0.12%) SARS-CoV-2 positive samples, achieving a 7.3-fold increase in throughput. DISCUSSION: Pooling approaches for SARS-CoV-2 testing allow a drastic increase in throughput while maintaining clinical sensitivity. We report the successful large-scale pooled screening of asymptomatic populations.

Anomalies of the fetal aortic arch: a novel sonographic approach to in-utero diagnosis.

OBJECTIVE: To describe a novel, sonographic approach for in-utero evaluation of normal and abnormal aortic arch. METHODS: Aortic arch was evaluated by imaging of the axial view of the upper fetal mediastinum. The normal left aortic arch was defined by the V-shaped appearance of the junction between the ductus arteriosus and aortic arch, with the trachea situated posteriorly. Right and double aortic arches were diagnosed when the great vessels appeared U-shaped, with intermediate location of the trachea. RESULTS: Between 1997 and 1999, 18 347 women were scanned in three prenatal centers, and pathological findings were prospectively recorded. In a retrospective analysis of the records, we identified 19 fetuses (0.1%) with atypical, U-shaped appearance, and no other structural abnormalities present. With the exception of one fetus with a ventricular septal defect, no congenital cardiac defects were present. Right aortic arch was found in 18 cases, while color Doppler made it possible to diagnose one case with double aortic arch, and one fetus was demonstrated as having Kommerell's diverticulum. In all 18 cases, a left descending aorta and left ductus arteriosus were present, the latter coursing to the left of the trachea, forming a loose partial vascular ring. All were asymptomatic at birth and early infancy. The fetus with double aortic arch that had a true vascular ring underwent early infantile correction. CONCLUSIONS: It is possible to diagnose right and double fetal aortic arch using prenatal ultrasound. The use of color Doppler facilitated in-utero evaluation of possible complications, such as true vascular ring.

A description of inappropriate hospital stays in selected in-patient services: a study of cases receiving social work services.

The number of discharges (63,303) from a university-affiliated medical center in Israel were reviewed. Eight percent of cases in three departments rcceivcd social work services. Patients experiencing inappropriate hospital stay (discharge delay) and who received social work services were characterized and compared with social work clients not experiencing delay. Discharge delay patients differed from other social work clients on key sociodemographic variables. Patients admitted because of "injury" were significantly more likely to experience delay than patients admitted because of "illness." "Waiting for community/institutional resources" was the most common reason for delay and discharge to an institutional setting increased the likelihood of delayed discharge. High risk factors were department-specific and should be studied in context. Results suggested the limited but positive impact of hospital-community collaborative strategies in reducing the incidence of delay over time.

Randomized comparison of J-shaped and straight atrial screw-in pacing leads.

OBJECTIVE: To study the importance of a J shape in atrial pacing leads. PATIENTS AND METHODS: We compared in a randomized controlled study acute and chronic results with 2 steroid-eluting, polyurethane, screw-in atrial lead models that differ only in shape. A total of 208 patients were randomized to have implantation of either a straight atrial lead (n = 105) or a J-shaped atrial lead (n = 103). Patients were followed up for 1 year. RESULTS: On implantation, there were no significant differences between leads in rates of failure to implant, implant measurements, number of attempts to achieve an acceptable position, and fluoroscopy times. Before discharge and at 3-month and 1-year follow-up, electrical measurements showed no statistical differences between leads. During the first year after implantation, there were 2.9% early dislodgments (< 1 week after implantation) and 2.9% late dislodgments in the straight lead group (5.9% rate of all dislodgments) vs no dislodgments in the J-shaped lead group (P = .01). There was a trend toward higher rates of exit block and lead malfunction in the J-shaped lead group. Rates of pericardial complications, subclavian/axillary thrombosis, and chronic atrial fibrillation were the same in both groups. CONCLUSIONS: Both leads appear to have an equally favorable performance profile for 1 year of follow-up. The J-shaped lead seems to be more stable and have fewer dislodgments, although it may have a somewhat higher malfunction rate.

Is fatigue in patients with multiple sclerosis related to autonomic dysfunction?

Time-dependent frequency decomposition of fluctuations in cardiovascular signals (heart rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of autonomic activity during transient and steady-state conditions. This method was applied during a change of position from supine to standing in patients with multiple sclerosis (MS) who experienced unexplained fatigue and in age-matched control subjects. No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects. Moreover, no difference was observed in very-low-frequency and low-frequency (related to sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to parasympathetic activity). The only spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power. Both these parameters provide an estimate of the sympathovagal balance. A significant increase in these two estimates on standing was observed in control subjects only, indicating possible impairment of the sympathovagal balance response to standing in patients with MS who experienced fatigue. The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated spectral estimates that reflect vagal activity. Therefore, the authors assumed that age-related reduction in vagal activity occurred earlier in patients with MS who experienced fatigue. This reduction could also explain the lack of increase in the sympathovagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Multiple adverse events with a dual chamber pacemaker.

The aim of the study was to evaluate our experience with Physiocor 400T, a dual chamber unipolar pacemaker manufactured by Sorin Biomedica. Between March 1993 and December 1994, 63 units of that model were implanted at our center. Patients were followed for 46 +/- 16 months. By the end of follow-up, 15 patients had died, 1 patient was lost to follow-up, and two units had been replaced for unrelated reasons. During follow-up the following phenomena had been observed: (1) Spontaneous backup reversion (VOO, 80 ppm) in 6 (9.5%) of 63 patients. In three patients this phenomenon was accompanied by concomitant ineffective pacing artifacts at 130 beats/min with very low pulse widths. (2) Unexpected battery depletion (EOL) occurred in 3 (5%) of 63 patients; two of the three occurred within weeks of routine evaluation that confirmed normal battery status. (3) Early elective replacement time (ERT) unpreceded by a gradual drop in magnet rate in 2 (3.2%) of 63 patients. (4) Total loss of telemetry without change in pacing mode in 1 (1.6%) of 63 patients. The estimated event-free 5-year survival of this model was 46%. In conclusion, 12 (19%) of 63 patients had adverse events with Physiocor 400T pacemakers. The potential risk of asynchronous pacing for prolonged periods and the risk of unexpected EOL warrants consideration of elective replacement of all remaining units.

Fetal aortic arch measurements between 14 and 38 weeks' gestation: in-utero ultrasonographic study.

OBJECTIVE: To establish in-utero reference ranges for fetal transverse aortic arch diameter (TAD) and distal aortic isthmus diameter (DAID) using high-resolution ultrasound techniques. DESIGN: A prospective, cross-sectional study was performed on 125 normal singleton pregnancies between 14 and 38 weeks' gestation. Transverse and diameter and DAID were measured by transvaginal ultrasonography until 17 weeks' gestation, and by abdominal ultrasound between 18 and 38 weeks' gestation. RESULTS: Transverse arch diameter as a function of gestational age was expressed by the regression equation TAD = -1.17 + 0.169 X GA, and DAID = -1.39 + 0.189 X GA; TAD and DAID are transverse aortic and distal aortic isthmus diameters expressed in millimeters and GA is gestational age in weeks. The correlation r = 0.924 and 0.938 was found to be highly statistically significant (P < 0.001) for TAD and DAID. The normal mean of TAD and DAID per week and the 95% prediction limits were also defined. CONCLUSIONS: The normative data established by us may be helpful in the prenatal diagnosis of congenital heart defects, including abnormal growth of the aortic arch.

Segmentary fetal branch pulmonary artery blood flow velocimetry: in utero Doppler study.

OBJECTIVE: To evaluate changes in human, fetal segmentary, pulmonary artery blood flow velocimetry throughout pregnancy. DESIGN: Ninety-nine women with a singleton, low-risk gestation between 14 and 37 weeks of pregnancy were selected to participate in a prospective, cross-sectional study. All fetuses were evaluated using power and color Doppler ultrasound. Flow velocity waveforms at three sites of the right pulmonary artery were obtained. The pulsatility index (PI) was calculated in the proximal, mid and distal segment of the pulmonary artery. Mean values and 95% confidence interval (CI) for each segment were determined in correlation with gestational age. RESULTS: A full study that included Doppler measurements of all three segments of the pulmonary artery was completed on 99 fetuses. The highest mean PI of 2.36 was obtained in the proximal segment of the right pulmonary artery (CI = 2.29-2.42), whereas in the mid and distal segments the mean PI decreased significantly to 1.57 (CI = 1.53-1.61) and 1.02 (CI = 1.0-1.0) (P < 0.001), respectively. Throughout gestation, the mean PI measurements in the proximal, middle and distal segments of the branch pulmonary artery increased slightly, but without statistical significance (r = 0.274, 0.248, 0.047), respectively; (P > 0.5). CONCLUSIONS: The data obtained suggests that pulmonary circulation maintains stable vascular resistance during gestation in the human fetus. However, the PI obtained from the separate segments of the branch pulmonary artery is unique and each differs from the other, reflecting the proximity to the heart and the peripheral impedance at each location.

Abnormalities of the fetal central veins and umbilico-portal system: prenatal ultrasonographic diagnosis and proposed classification.

OBJECTIVES: Anomalies of the fetal venous system are poorly documented and their pathogenesis is not well understood. The present study was undertaken to review the spectrum of fetal central veins and umbilico-portal system anomalies, and to propose a classification system. METHODS: A 7-year restrospective survey was conducted. RESULTS: Nineteen fetuses showed abnormal connection between central veins and the fetal heart. Three fetuses showed abnormal connections of the cardinal veins, two of which had interruption of the inferior vena cava, and one had isolated persistent left superior vena cava. Anomalies of pulmonary veins were seen in four fetuses: in two with asplenia syndrome, a vertical confluent pulmonary artery was observed. In a further two cases total anomalous pulmonary venous connections were found. Abnormalities of the umbilical vein (UV) were seen in 10 cases; seven had persistent right UV, and three had a spectrum of anomalies: One had abnormal connections of the UV to the left iliac vein associated with agenesis of the ductus venosus (DV) and hydrops fetalis. One case showed in utero occlusion of the DV by echogenic foci that resulted in a persistent left proximal UV and porto-systemic shunt. One case had obliteration of the DV secondary to in utero fetal hepatic fibrosis. Abnormalities of the vitelline veins or portal system were demonstrated in two cases. One had a left porto-systemic shunt which resolved spontaneously at 3 months of age, and one had secondary partial occlusion of the left portal system with liver echogenicities and direct communication of the UV with the right atrium. None of the 19 cases had an abnormal karyotype or evidence of in utero infection. CONCLUSIONS: Detection of various fetal vein anomalies in utero is feasible. The anomalies vary according to embryologic precursors or etiology. Two major mechanisms seem to be involved in the genesis of fetal vein anomalies: in most cases primary maldevelopment of the venous system occurs, while in the minority secondary anomalies from possible thromboembolic events or systemic disease may play a role.

Quality of life in multiple sclerosis: development and validation of the 'RAYS' scale and comparison with the SF-36.

OBJECTIVE: To develop a self-administered rating scale for quantifying quality of life (QoL) in multiple sclerosis (MS) patients. METHODS: The RAYS scale items were derived from a source of 600 questions composed by our Centre's experts from commonly used instruments that assess physical, psychological, and social-familial dimensions. Prior to finalization of the RAYS QoL, candidate items were administered to 15 health rehabilitation professionals. Clarity, importance, relevance and specificity were graded for each item by every professional independently. Items chosen for the final version were graded as good or excellent on all these aspects. The Medical Outcome Study Short Form-36 (SF-36) was used to compare health appraisal with the RAYS scale. RESULTS: Each of the three subscales of the RAYS covers a different dimension (physical, psychological, and social-familial) and each includes 15 self-report items scored from 1 (best) to 4 (worse), focusing on the preceding week. Validation was achieved through administration of the scale to 50 randomly selected MS patients and to 50 age, sex-, education- and family status-matched healthy controls. All RAYS dimensions among MS patients reached a Cronbach's coefficient alpha > 0.8. Mean values for all dimensions were greater in patients than in controls (P < 0.002). Patients scored below norms for the general population in the majority of the SF-36 subscales (on average 32% lower). Significant correlation was found between the two scales especially in the physical and social functioning subscales. CONCLUSION: The RAYS scale demonstrated high internal consistency and significant discriminative value, and is thus a suitable disease-specific tool for measuring QoL in MS.

Pregnancy during residency--an Israeli survey of women physicians.

The objective is to assess the impact of workload on pregnancy among women physicians in public hospitals in Israel. A self-administered, cross-sectional study of pregnancies among women physicians in public hospitals was conducted. An 82-item questionnaire was mailed to women physicians in the three largest university hospitals in Israel. The questionnaire assessed demographic data, pregnancy course, perceived stress, and complications during pregnancy. Response rate was 52% (207/400). The complication rates were compared with rates in the Jewish population and expressed as mean +/- SD. Mean number of pregnancies during residency was 1.3 +/- 1.2. Mean age at the first delivery was 27 +/- 3.2 years. There was a significant difference in the rates of stillbirth (32/1000 births versus 3.7/1000, p < 0.001) and premature delivery (12.4% versus 7.6%, p = 0.0014) between women physicians and the general population. There was no significant difference in the proportion of spontaneous abortions (12.7%), pregnancy induced hypertension (3.2%), hyperemesis gravidarum (3.2%), and diabetes (1%). Seven percent of women physicians changed their specialty due to pregnancy while in residency. Our results suggest that working long hours in a stressful occupation in a hospital environment has an adverse effect on pregnancy course and is associated with increased rates of stillbirth and premature delivery.

Does the coronary care unit improve prognosis of patients with acute myocardial infarction? A thrombolytic era study.

AIMS: The purpose of our study was to examine and compare the prognosis of acute myocardial infarction patients hospitalized in an intensive coronary care unit and in an internal medicine ward, in the era of reperfusion therapy, and to identify factors associated with the observed outcomes. METHODS AND RESULTS: Patients hospitalized for acute myocardial infarction during the period 1994-1997 at the Sheba Medical Center, Tel Hashomer, Israel (n=2114), were grouped according to the hospital department in which they were treated: the intensive coronary care unit (n=1443, 68.3%) or an internal medicine ward (n=671, 31.7%). Baseline characteristics, comorbidity, hospital course, use of procedures and 30-day mortality were compared between the groups. Stepwise logistic regression was used to identify the factors associated with 30-day mortality. Crude 30-day mortality rates were 5.4% among all patients hospitalized in the intensive coronary care unit compared with 15.9% for all patients in an internal medicine ward (P<0.001); in a subgroup of patients aged 70 years and above these rates were 11.0% and 21.0%, respectively (P<0. 001). Among the independent predictors of the 30-day mortality identified in multivariate analysis was treatment only in an internal medicine ward (odds ratio: 1.48; 95% confidence interval: 1. 00-2.18). Reperfusion therapy was independently associated with a 53% reduction in 30-day mortality. CONCLUSIONS: Our findings emphasize the importance of the treatment of acute myocardial infarction in the setting of intensive coronary care units in the thrombolytic era, in order to ensure early access to advanced diagnostic and therapeutic options for all patients, including the elderly.

Pregnancy and multiple sclerosis: a 2-year experience.

OBJECTIVE: To present our experience with management of parturients with multiple sclerosis and to examine the role of intravenous immunoglobulin (IVIg) in the prevention of postpartum exacerbations of the disease. METHODS: Fifteen patients with multiple sclerosis with a relapsing-remitting course were followed during pregnancy and 6 months postpartum. To prevent postpartum exacerbations, 14 of the patients had received IVIg after delivery. RESULTS: None of the patients who received postpartum IVIg relapsed during the 6 months after delivery. None of the observed obstetric complications nor the operative deliveries could be related to the coexistence of multiple sclerosis. CONCLUSION: Postpartum IVIg treatment is beneficial in preventing acute childbirth-associated exacerbations in patients with relapsing-remitting multiple sclerosis. Furthermore, this disease does not seem to increase obstetric complications.

Newly implemented health system reform in Israel: physicians' attitudes.

OBJECTIVE: To explore the attitudes of Israeli physicians towards the feasibility and potential consequences of the newly implemented health care reform. DESIGN: Physicians' attitudes were examined soon after the enactment of a National Health Insurance Law, the first element of the reform to be implemented. SETTING: A nationwide mail survey. SUBJECTS: A random sample of 2000 practicing physicians. MAIN OUTCOME MEASURES: Attitudes towards the health care system prior to the reform; predicted effects of the reform on health care and medical practice. RESULTS: Most of the respondents think that the system requires a change. Quality of community-based care is expected to increase, in contrast to hospital care. The reform is believed to exert an adverse effect on medical practice. Attitude is significantly influenced by practice setting and speciality: community setting and general practice correlate with less desire for a major change. Specialists believe that reform elements which will shift the balance towards the hospitals will have the greatest benefit on the health system. GPs, compared to specialists, are more optimistic regarding quality and accessibility of services (P<0.01). CONCLUSIONS: Our survey suggested that Israeli physicians favor a change in the health care system, despite a perceived adverse effect of the reform on medical practice. Since the reform is believed to shift the balance from the hospitals to the community, respondents support changes that will compensate for the imbalance.

Superior mesenteric artery blood flow velocimetry: cross-sectional Doppler sonographic study in normal fetuses.

Our objectives were to describe the flow velocity waveform of the fetal superior mesenteric artery and to establish a nomogram for its pulsatility index. In a cross-sectional study using color Doppler ultrasonography, superior mesenteric artery flow velocimetry was investigated prospectively in 96 healthy fetuses of between 14 and 37 weeks of gestation. In normal fetuses the pulsatility index measurements showed a slight but insignificant increase over the course of gestation (r = 0.26; P > 0.5). The lowest mean +/- standard deviation for pulsatility index in the superior mesenteric artery was 1.86 +/- 0.45 (95% confidence interval 1.67-2.06), recorded between 18 and 21 weeks' gestation. Thereafter the pulsatility index increased to 1.94 +/- 6.4 (95% confidence interval 1.74-2.8) at 22 to 25 weeks, and from weeks 26 to 29 it increased to 2.18 +/- 0.52 (95% confidence interval 1.91-2.46). During the third trimester and at term, the mean pulsatility index of 2.23 +/- 0.32 (95% confidence interval 1.43-3.03) did not change significantly with gestational age. In normal fetuses, except for the early stages, a relatively stable vascular resistance of the intestinal circulation was found. The application of this nomogram in clinical practice may facilitate evaluation of intestinal perfusion in compromised fetuses with blood flow centralization.

Peripheral right pulmonary artery blood flow velocimetry: Doppler sonographic study of normal and abnormal fetuses.

The knowledge of fetal lung circulation in normal and abnormal human fetuses is limited. Our objectives were to assess normal values for flow velocity waveforms in the fetal pulmonic circulation and to test the hypothesis that Doppler velocimetry can predict lung hypoplasia. In a cross-sectional study, peripheral right pulmonary artery flow velocimetry was investigated prospectively in 96 healthy fetuses between 14 and 37 weeks' gestation and four fetuses with abnormalities known to induce lung hypoplasia. The pulsatility index was used to quantify the velocity waveforms. In normal fetuses the mean pulsatility index in the peripheral right pulmonary artery was low, being equivalent to that corresponding to 14 to 17 weeks' gestation (2.89; confidence interval = 2.35 to 3.42), increasing at midgestation to 3.44, with a confidence interval of 3.04 to 3.83; P < 0.01. Thereafter, during the late second and third trimesters the mean pulsatility index did not change significantly with GA, being 3.66 (confidence interval = 3.04 to 4.04) at term. In fetuses with proven lung hypoplasia, the pulsatility index measurements were within the 95% confidence limits of those for normal fetuses. In a normal pregnancy, except for the early stages, a relatively stable high vascular resistance of the fetal pulmonary circulation was found. Our preliminary data suggest that the pulsatility index of the lung circulation cannot be used as an indicator of lung hypoplasia.

Preadmission psychosocial screening of older orthopedic surgery patients: evaluation of a Social Work Service.

A preadmission social work intervention was evaluated for impact on length of hospital stay (LOS) and patient satisfaction. Psychosocial issues related to function and post-discharge needs were assessed at an exploratory level. A modified post-test only control group design was used. Study group patients were screened before hospitalization and offered services on admission. Control group patients received standard care. Study group patients were significantly more satisfied with services but impact on length of stay was not demonstrated with one possible exception. Post-operative complications were significantly related to longer LOS; however, unlike control group patients, study group patients with complications did not have significantly longer LOS. Women and those limited in preadmission physical function were most likely to report insufficient help after discharge. A more intensive preadmission intervention is recommended to improve impact on LOS and informal support system involvement, while future outcome studies would clarify the nature of service gaps and high risk groups.